The abnormalities in the regulation of lipid biosynthesis in tissue culture cell lines will be studied in cells derived from genetically abnormal human subjects and compared with cells from normal subjects. The specific genetic variants will be abetalipoproteinemia, and homozygous familial hypercholesterolemia. In addition to the fibroblast and lymphoid cell lines, it is planned to grow epithelial cells in culture. The identification of receptors for low density lipoproteins wll be carried out in freshly obtained lymphocytes, phytohemagglutinin stimulated lymphocytes, as well as in the cell lines. The regulation of intracellular cholesteryl ester metabolism will be studied in epithelial cells in culture. Additional studies of cholesterol balance will be performed in patients with abetalipoproteinemia. The tocopherol content of platelets in these patients will be compared with values in normal subjects, patients with high tocopherol intake, and those deficient in tocopherol. Methods for measuring tocopherol content of polymorphonuclear leukocytes and of lymphocytes will be established.